TUSC1

Chr 9

tumor suppressor candidate 1

Also known as: CCDC89B, TSG-9, TSG9

NCBI Gene: 286319ENSG00000198680UniProt: Q2TAM9OMIM: 610529

The TUSC1 protein functions as a tumor suppressor that is downregulated in lung cancers. Mutations in this gene cause autosomal recessive intellectual disability with macrocephaly, seizures, and distinctive facial features, typically presenting in early childhood. This gene shows low constraint against loss-of-function variants in the general population.

OMIMResearchSummary from RefSeq
MultiplemechanismLOEUF 1.74
Clinical Summary— TUSC1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
74 unique Pathogenic / Likely Pathogenic· 60 VUS of 142 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.74LOEUF
pLI 0.043
Z-score 0.53
OE 0.67 (0.27–1.74)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.51Z-score
OE missense 1.14 (0.98–1.33)
119 obs / 104.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.67 (0.27–1.74)
0≤0.351.4
Missense OE1.14 (0.98–1.33)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 2 / 3.0Missense obs/exp: 119 / 104.2Syn Z: 0.01
DN
0.6455th %ile
GOF
0.6444th %ile
LOF
0.4331th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

142 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic68
Likely Pathogenic6
VUS60
Likely Benign8
68
Pathogenic
6
Likely Pathogenic
60
VUS
8
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
68
0
68
Likely Pathogenic
0
0
6
0
6
VUS
0
53
7
0
60
Likely Benign
0
4
4
0
8
Benign
0
0
0
0
0
Total057850142

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TUSC1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients